Pancreatic adenocarcinoma is the fifth leading cause of cancer death in the United States. The etiology of this malignancy is large unknown. Advancing age, male gender and smoking are established risk factors, while chronic pancreatitis and diabetes may be as well. The prognosis for patients with pancreatic cancer is poor, with reported 1 year survival rates between 5% and 10%.
There is considerable evidence to support a central role for cholecystokinin (CCK)* in human pancreatic cancer. The influence of endogenous hormones is well-described for several human malignancies including breast, ovary and prostate. Generally, the hormones implicated are important in both the health and disease of their target organ. CCK is an important mediator in the growth of the normal pancreas. Animal studies in which exogenous CCK was administered or endogenous CCK levels were manipulated documented pancreatic hyperplasia, dysplasia and the production of frank malignancies. Similar studies, following the induction of pancreatic tumors, suggest that CCK administration accelerates the growth of malignant compared to uninvolved tissue. In human cancer cell lines and xenografted human tumors, CCK promotes the growth of pancreatic adenocarcinoma.
Two CCK receptors have been characterized and cloned in animal and human studies, CCK-A and CCK-B. These receptors share structural homology and can be differentiated based on their binding affinities for CCK and another related gastrointestinal hormone, gastrin. The CCK-A receptor has an affinity for CCK which is 1000-fold greater than for gastrin while the CCK-B receptor exhibits equivalent affinities for either peptide.
The identification of a specific marker for pancreatic cancer would be of substantial diagnostic, and potentially therapeutic benefit. There remains a need for compositions, kits and methods for screening individuals and identifying pancreatic cancer cells. There remains a need for compositions and a method of imaging pancreatic cancer cells. There remains a need for compositions and methods for treating individuals who have pancreatic cancers.